EFFECTS OF AGE ON STEROID BINDING AND MORPHOLOGY IN VARIOUS REGIONS OF RAT BRAIN

Abstract

Glucocorticoid receptor levels in the cytosol of hypothalamus, hippocampus, frontal cortex and cerebellum were determined in 5, 14 and 27 month male Fischer 344 rats. There were no changes between 5 and 14 months, but the number of {lcub}('3)H{rcub}dexamethasone binding sites was reduced about 50% in the hypothalamus and hippocampus of 27 month old rats, as compared to the younger animals. The number of binding sites did not change with age in frontal cortex and cerebellum. Adrenalectomy did not alter the level of dexamethasone binding in old or young animals, and the affinity of the receptor did not change with age in any of the brain regions examined. A single high-affinity binding component with a K(,d) of 3 x 10('-10) was detected in hypothalamus and hippocampus. Cerebral cortex had two binding components with a Kd's 3 x 10('-10) and 8.5 x 10('-9) respectively. The cerebellum had only a low affinity binding component with a K(,d) of 7 x 10('-9).;Estradiol receptor levels in the cytosol of hypothalamus, amygdala, frontal cortex and cerebellum were determined in 5, 14 and 27 month female Fischer 344 rats. There were no changes between 5 and 14 months, but the number of {lcub}('3)H{rcub}estradiol binding sites was reduced about 40% in all regions of brain studied in 27 month old rats, as compared to the younger animals. A single high-affinity binding component was present in these regions with a K(,d) of 1.55-1.85 x 10('-9). The affinity of the receptor did not change with age in any of the regions of brain examined.;Neuronal counts and the volume of various nuclear groups of the hypothalamus were examined in male and female Fischer 344 rats aged 5, 14 and 27 months. The nuclear groups tested include supraoptic, paraventricular, suprachiasmatic, dorsomedial, ventromedial and arcuate. There was no change with age nor was there evidence of sexual dimorphism in the volume of any of the nuclear groups studied. Neuronal numbers diminished approximately 20% in the supraoptic and paraventricular nuclei, and 30% in the dorsomedial nucleus of 27 month old rats of both sexes compared to 5 and 14 month animals. In the suprachiasmatic nucleus, neuronal numbers dropped 17% in 14 month females and 48% in 27 month females compared to 5 month animals. In the males, neuronal numbers dropped 27% in 27 month old animals compared to 5 and 14 month animals. 27 month old males lost approximately 35% of their neurons in the ventromedial and 22% in the arcuate nucleus compared to the numbers present in 5 and 14 month animals, whereas females lost nearly 50% of their neurons at 27 months in both these regions.;These data indicate that the loss in numbers of steroid binding sites may be due to a loss in numbers of hormone-responsive neurons.;Electron microscopy of these nucelar regions was quantified morphometrically in 6 and 26 month old Fischer 344 rats. The volume density of neuronal nuclei did not change with age in any of these regions. The volume density of neuronal nucleoli decreased from 30-60% in all nuclear groups except for the supraoptic nucleus, where it increased slightly. The volume density of neuronal lipofuscin increased 4-25 fold in the various regions of hypothalamus, with a 1-4 fold increase in numerical density of lipofuscin. The numerical density of mitochondria, dense bodies and secretor-granules decreased in nearly all regions of the hypothalamus, concomitant with a decrease in the surface density of Golgi apparatus and rough endoplasmic reticulum. These data are consistent with a state of decreased biosynthetic and metabolic activity in these senescent neurons.;The data presented here are used to support the possibility that the hypothalamus controls a number of the neuroendocrine changes associated with aging. Additionally, an anatomical model of climacteric in the female rat is proposed and discussed.